The invention relates to a method for strengthening a vessel wall e.g., by irradiation with an energy source, or by inducing injury to the vessel wall, such that the injury initiates a cascade of events leading to fibrosis and a thickening of the vessel wall. In addition to an energy source, a photoactivable agent can also be used such that the energy activates the photoactivable agent which causes structural changes in the vessel wall. More specifically, the invention relates to treating aneurysms using UV radiation with a psoralen compound.
There are two basic types of blood vessels, arteries and veins, which can be distinguished by their structural components. Arteries and veins both have several distinct layers which are arranged coaxially. In arteries, the layers include an inner coat or endothelial layer (intima), an internal elastic lamina, a middle layer (media), and an outer layer (adventitia). Like arteries, veins include an inner layer (intima), a middle layer (media) and an outer layer (adventitia), but the layers are not as thick as in arteries, and provide less structural rigidity.
Both arteries and veins are elastic, and are capable of limited deformation in response to pressure changes. When a diseased blood vessel is exposed to hypertension, dilation may occur at various localized regions. Typically these dilatations are produced at the region in the vessel wall which is weakest, whether inherently or as a result of disease or trauma. As the dilatation progresses, a more pronounced widening or sac, called an aneurysm, is produced, which may burst. A large aneurysm can form clots secondary to a reduction in blood flow in the aneurysmal sac. These chits may emobilize and block distal arteries.
Arteriosclerosis and cystic medial necrosis are two common causes of aneurysms of the thoracic and abdominal aorta. Thoracic aneurysms commonly compress and impact surrounding body structures as they expand. They may impact into the lungs, the spinal column, or the gastrointestinal tract.
Berry aneurysms are congenital defects which occur in cerebral arteries, most commonly at the junctions of vessels in the circle of Willis. These aneurysms appear to be related to defects in the muscular coat of the vessels. Rupture is common, resulting in intracranial hemorrhage.
Other aneurysms include aortic aneurysms, especially abdominal aortic aneurysms (AAA), which are characterized by transmural aortic wall degeneration leading to dilatation, progressive growth, and eventual rupture.
Treatment of aneurysms typically involves either surgical intervention, such as in thoracic or abdominal aneurysms, or coil ablation, such as in aneurysms of the brain. Excision of the aneurysm, and anastomosis of the vessel may be performed, often using a replacement vessel or an artificial prosthesis. Alternatively, a supporting structure such as a stent or other intravascular device may be implanted into the vessel to relieve stress. Examples of stents, include those disclosed in U.S. Pat. No. 4,655,771 issued to Wallsten et al., With the stent positioned at the treatment site, the stent can be radially expanded into a conforming surface in contact with a blood vessel wall. The stents may also be covered with a film or a sheath such as, polytetrafluoroethylene (PTFE) as described in U.S. Pat. No. 5,788,626 to Thompson, et al.
Prostheses used to treat aneurysms are also described in, for example, U.S. Pat. No. 4,681,110 issued to Wiktor et al., Wiktor et al., discloses a flexible tubular liner that is inserted into the aorta to treat aortic aneurysms. The liner has flexible plastic strands designed to elastically expand against the aneurysm and to direct blood flow past the aneurysm.
While these methods achieve the general goal of reducing fatality, these methods have a drawback in that the aneurysm remains a weak area in the blood vessel wall. Mohr et al. in U.S. Pat. No. 5,921,954 describe treating aneurysms using hardening and softening agents, (e.g. collagen), which are applied at the site of the aneurysm. A radio frequency energy is then used to harden the agent and cover the weak region of the blood vessel wall.
Prophylactic methods are used to prevent the formation of aneurysms and rely on reducing the blood pressure, in an effort to reduce mechanical stress on the vasculature. These methods involve using drugs which can have undesirable side effects, e.g., cause kidney or liver damage.
Drugs, such as tetracyclines have been used to prevent abnormal vascular dilation, as described in U.S. Pat. No. 5,834,449 issued to Thompson et al. The tetracycline compounds protect the elastic fibers of the media by selectively inhibiting the elastolytic activity in this region thereby preventing its expansion.
While these methods are effective in treating aneurysms, these methods do not improve the overall structure of the blood vessel which still remains weak at the site of the aneurysm and may still be susceptible to rupture. Accordingly, one purpose of this invention is to provide a method of strengthening a blood vessel.